Pregnenolone sulfate induces NMDA receptor dependent release of dopamine from synaptic terminals in the striatum.

Journal of Neurochemistry
Matthew T WhittakerDavid H Farb

Abstract

Neuromodulators that alter the balance between lower-frequency glutamate-mediated excitatory and higher-frequency GABA-mediated inhibitory synaptic transmission are likely to participate in core mechanisms for CNS function and may contribute to the pathophysiology of neurological disorders such as schizophrenia and Alzheimer's disease. Pregnenolone sulfate (PS) modulates both ionotropic glutamate and GABA(A) receptor mediated synaptic transmission. The enzymes necessary for PS synthesis and degradation are found in brain tissue of several species including human and rat, and up to 5 nM PS has been detected in extracts of postmortem human brain. Here, we ask whether PS could modulate transmitter release from nerve terminals located in the striatum. Superfusion of a preparation of striatal nerve terminals comprised of mixed synaptosomes and synaptoneurosomes with brief-duration (2 min) pulses of 25 nM PS demonstrates that PS increases the release of newly accumulated [3H]dopamine ([3H]DA), but not [14C]glutamate or [3H]GABA, whereas pregnenolone is without effect. PS does not affect dopamine transporter (DAT) mediated uptake of [3H]DA, demonstrating that it specifically affects the transmitter release mechanism. The PS-induced [3...Continue Reading

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Citations

Sep 6, 2008·The Journal of Pharmacology and Experimental Therapeutics·G Sadri-VakiliD H Farb
Jul 7, 2014·Psychopharmacology·Conor C SmithDavid H Farb
Oct 3, 2013·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christian Harteneck
Apr 9, 2013·Frontiers in Neuroendocrinology·Flavia di MichelePatrizia Longone
Sep 5, 2012·The Journal of Steroid Biochemistry and Molecular Biology·Marie BicikovaRichard Hampl
Jun 29, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Anna KrohmerBela Szabo
Feb 10, 2019·Molecular Brain·Rongyi ZhouYuchen Song
Apr 27, 2019·Frontiers in Endocrinology·Marcia H RatnerDavid H Farb
Jul 28, 2019·Molecular Genetics & Genomic Medicine·Eva Albertsen MaltHilde Loge Nilsen
Oct 22, 2017·Neuroscience and Biobehavioral Reviews·Tatiana BarichelloJoao Quevedo

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